Abstract: Salt water intrusion is a widespread problem in coastal tidal estuary, in this paper, the compiled source code of Delft 3D 4.01.01 was used to establish a two-dimensional mathematical model of salinity in the estuary of the Yangtze River to study the response mechanism between runoff into the sea and salt water intrusion. The result shows that the Delft 3D 4.01.01 source code is qualified to simulate the hydrodynamic salinity distribution in the Yangtze Estuary with only 10%~15% verification errors. Otherwise, the case is evident that saltwater intrusion is related with the runoff. When the runoff at Datong station is 5000 m3/s, the saltwater intrusion occurred both in the South and the North Branch. As the runoff increases, the fresh water area expands toward downstream from the right bank of South Branch. When the flow rate exceeds 30000 m3/s, salt water intrusion no longer occurs in the South Branch, so the security of water intake can be guaranteed. In windy day, there will be obvious salt water intrusion with salinity concentration more than 3.5 ppt, in calm weather, the trend of saltwater intrusion become weak, and the salinity concentration in the South Branch generally meet irrigation water standard (2.2 ‰).